scholarly journals 22(R)-hydroxycholesterol for dopaminergic neuronal specification of MSCs and amelioration of Parkinsonian symptoms in rats

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Manisha Singh ◽  
Manish Jain ◽  
Samrat Bose ◽  
Ashutosh Halder ◽  
Tapas Chandra Nag ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Dental Pulp ◽  
Neuronal Cells ◽  
Human Mesenchymal Stem Cells ◽  
Wistar Rat ◽  
Human Mscs ◽  
In Vitro Differentiation

AbstractOxysterols play vital roles in the human body, ranging from cell cycle regulation and progression to dopaminergic neurogenesis. While naïve human mesenchymal stem cells (hMSCs) have been explored to have neurogenic effect, there is still a grey area to explore their regenerative potential after in vitro differentiation. Hence, in the current study, we have investigated the neurogenic effect of 22(R)-hydroxycholesterol (22-HC) on hMSCs obtained from bone marrow, adipose tissue and dental pulp. Morphological and morphometric analysis revealed physical differentiation of stem cells into neuronal cells. Detailed characterization of differentiated cells affirmed generation of neuronal cells in culture. The percentage of generation of non-DA cells in the culture confirmed selective neurogenic potential of 22-HC. We substantiated the efficacy of these cells in neuro-regeneration by transplanting them into Parkinson’s disease Wistar rat model. MSCs from dental pulp had maximal regenerative effect (with 80.20 ± 1.5% in vitro differentiation efficiency) upon transplantation, as shown by various behavioural examinations and immunohistochemical tests. Subsequential analysis revealed that 22-HC yields a higher percentage of functional DA neurons and has differential effect on various tissue-specific primary human MSCs. 22-HC may be used for treating Parkinson’s disease in future with stem cells.

PTX3 secreted by human adipose-derived stem cells promotes dopaminergic neuron repair in Parkinson's disease via inhibiting apoptosis

2021 ◽  
Author(s):  
Changlin Lian ◽  
Qiongzhen Huang ◽  
Xiangyang Zhong ◽  
Zhenyan He ◽  
Boyang Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Brain Slices ◽  
Human Mesenchymal Stem Cells ◽  
Substantia Nigra Pars Compacta ◽  
Therapeutic Effects ◽  
Label Free

Abstract Background Adipose-derived human mesenchymal stem cells (hADSCs) transplantation has recently emerged as a promising method in the treatment of Parkinson's disease (PD), however, the mechanism underlying has not been fully illustrated. Methods In this study, the therapeutic effects of the striatum stereotaxic injected hADSCs in 6-OHDA-induced mouse model were evaluated. Furthermore, an in vitro model of PD was constructed using tissue-organized brain slices. And the therapeutic effect was evaluated by co-culture of hADSCs and 6-OHDA-constructed brain slice. Within the analysis of hADSCs' exocrine proteins through RNA-seq, Human protein cytokine arrays and label-free quantitative proteomics, key extracellular factors were identified in hADSCs secretion environment.The degeneration of DA neurons and apoptosis were measured in PD samples in vivo and vitro models, and the beneficial effects were evaluated through quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot,Fluoro-Jade C, Tunel assay and immunofluorescence analysis. Results In this study, we discovered that hADSCs protected the dopaminergic (DA) neurons in vivo and vitro models.we identified Pentraxin3 (PTX3) as a key extracellular factor in hADSCs secretion environment. Moreover, we found that human recombinant Pentraxin3 (rhPTX3) treatment could rescue the physiological behaviour of the PD mice in-vivo, as well as prevent DA neurons from death and increase the neuronal terminals in the Ventral tegmental area (VTA) + substantia nigra pars compacta (SNc) and striatum (STR) on the PD brain slices in-vitro. Furthermore, within testing on the pro-apoptotic markers of PD mice brain following the treatment of rhPTX3, we found that rhPTX3 can prevent the apoptosis and the degeneration of DA neurons. Conclusions Overall, the current study investigated that PTX3, a hADSCs secreted protein, played a potential role in protecting the DA neurons from apoptosis and degeneration in PD progression as well as improving the motor performances in PD mice to give a possible mechanism of how hADSCs works in the cell replacement therapy in PD. Importantly, our study also provided potential translational implications for the development of PTX3-based therapeutics in PD.

In vitro differentiation into insulin-producing β-cells of stem cells isolated from human amniotic fluid and dental pulp

2013 ◽  
Vol 45 (8) ◽  
pp. 669-676 ◽  
Author(s):  
Gianluca Carnevale ◽  
Massimo Riccio ◽  
Alessandra Pisciotta ◽  
Francesca Beretti ◽  
Tullia Maraldi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Dental Pulp ◽  
In Vitro Differentiation ◽  
Β Cells ◽  
Human Amniotic Fluid

Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 4120-4126 ◽  
Author(s):  
Xiao-Xia Jiang ◽  
Yi Zhang ◽  
Bing Liu ◽  
Shuang-Xi Zhang ◽  
Ying Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Human Mesenchymal Stem Cells ◽  
Interleukin 4 ◽  
Human Mscs ◽  
Gm Csf ◽  
Macrophage Colony ◽  
And Function

AbstractMesenchymal stem cells (MSCs), in addition to their multilineage differentiation, have a direct immunosuppressive effect on T-cell proliferation in vitro. However, it is unclear whether they also modulate the immune system by acting on the very first step. In this investigation, we addressed the effects of human MSCs on the differentiation, maturation, and function of dendritic cells (DCs) derived from CD14+ monocytes in vitro. Upon induction with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), MSC coculture could strongly inhibit the initial differentiation of monocytes to DCs, but this effect is reversible. In particular, such suppression could be recapitulated with no intercellular contact at a higher MSC/monocyte ratio (1:10). Furthermore, mature DCs treated with MSCs were significantly reduced in the expression of CD83, suggesting their skew to immature status. Meanwhile, decreased expression of presentation molecules (HLA-DR and CD1a) and costimulatory molecules (CD80 and CD86) and down-regulated IL-12 secretion were also observed. In consistence, the allostimulatory ability of MSC-treated mature DCs on allogeneic T cells was impaired. In conclusion, our data suggested for the first time that human MSCs could suppress monocyte differentiation into DCs, the most potent antigen-presenting cells (APCs), thus indicating the versatile regulation of MSCs on the ultimate specific immune response.

scholarly journals Biofunctionalised bacterial cellulose scaffold supports the patterning and expansion of human embryonic stem cell-derived dopaminergic progenitor cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Miranda Robbins ◽  
Venkat Pisupati ◽  
Roberta Azzarelli ◽  
Samer I. Nehme ◽  
Roger A. Barker ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Bacterial Cellulose ◽  
Progenitor Cells ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem

Abstract Background Stem cell-based therapies for neurodegenerative diseases like Parkinson’s disease are a promising approach in regenerative medicine and are now moving towards early stage clinical trials. However, a number of challenges remain including the ability to grow stem cells in vitro on a 3-dimensional scaffold, as well as their loss, by leakage or cell death, post-implantation. These issues could, however, be helped through the use of scaffolds that support the growth and differentiation of stem cells both in vitro and in vivo. The present study focuses on the use of bacterial cellulose as an in vitro scaffold to promote the growth of different stem cell-derived cell types. Bacterial cellulose was used because of its remarkable properties such as its wettability, ability to retain water and low stiffness, all of which is similar to that found in brain tissue. Methods We cultured human embryonic stem cell-derived progenitor cells on bacterial cellulose with growth factors that were covalently functionalised to the surface via silanisation. Epifluorescence microscopy and immunofluorescence were used to detect the differentiation of stem cells into dopaminergic ventral midbrain progenitor cells. We then quantified the proportion of cells that differentiated into progenitor cells and compared the effect of growing cells on biofunctionalised cellulose versus standard cellulose. Results We show that the covalent functionalisation of bacterial cellulose sheets with bioactive peptides improves the growth and differentiation of human pluripotent stem cells into dopaminergic neuronal progenitors. Conclusions This study suggests that the biocompatible material, bacterial cellulose, has potential applications in cell therapy approaches as a means to repair damage to the central nervous system, such as in Parkinson’s disease but also in tissue engineering.

scholarly journals Evaluation of Priming Efficiency of Forskolin in Tissue-Specific Human Mesenchymal Stem Cells into Dopaminergic Neurons: An In Vitro Comparative Study

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2058
Author(s):  
Manisha Singh ◽  
Pardeep Kumar Vaishnav ◽  
Amit Kumar Dinda ◽  
Sujata Mohanty
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Calcium Ion ◽  
Dopaminergic Neurons ◽  
Neuronal Cells ◽  
Human Mesenchymal Stem Cells ◽  
Generate Functional ◽  
Efficient Manner ◽  
Protein Levels

Background: Human mesenchymal stem cells (hMSC) can be derived from various tissue sources and differentiated into dopaminergic (DAergic) neurons using various types of inducers. There are several strategies that have been reported to generate functional dopaminergic neuronal cells from hMSCs in the most efficient manner possible. However, this area is still under extensive research. In this study, we aim to compare hMSCs derived from bone marrow (BM), adipose tissue (AD) and dental pulp (DP) to generate functional dopaminergic neurons, using FGF2 and forskolin. Post-differentiation, multiple factors were used to characterize the cells at morphological, morphometric, ultra-structural, mRNA and protein levels for various markers (Nestin, NF, MAP2, Tuj1, TH, DAT, PitX3, Ngn2, Kv4.2, SCN5A). Cells’ functionality was studied by calcium ion imaging, along with the amount of dopamine secreted by the cells in the culture medium. Results: Data analysis revealed that forskolin has comparable effect on BM- and AD-derived MSC (28.43% and 29.46% DAergic neurons, respectively), whereas DP-MSC (42.78 ± 1.248% DAergic neurons) show better outcome in terms of efficient generation of DAergic neuronal cells, expression of neuronal associated markers, dopamine release and calcium ion efflux. Ultra-structural studies by SEM and TEM also revealed a substantial change in both cellular morphology and composition of cellular organelles. It was observed that AD-MSCs showed the best neuronal features, at morphological, gene, and protein levels upon induction with the above-mentioned induction cocktail. Conclusion: It may be concluded that a combination of FGF2 and forskolin yields functionally active dopaminergic neuronal cells in vitro, with highest percentage of the same from AD-MSCs, as compared to that in BM-MSCs and DP-MSCs. The outcomes and comparative evaluation provide a substantial platform for further studies on molecular pathways involved in the process of DAergic neurogenesis in individual cases.

Polyphenols and Stem Cells for Neuroregeneration in Parkinson’s Disease and Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 27 ◽  
Author(s):  
Shweta Goyal ◽  
Brashket Seth ◽  
Rajnish Kumar Chaturvedi
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Amyotrophic Lateral Sclerosis ◽  
Stem Cell ◽  
Motor Neurons ◽  
Dopaminergic Neurons ◽  
Dietary Polyphenols ◽  
Lateral Sclerosis

: Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS) are neurological disorders, pathologically characterized by chronic degeneration of dopaminergic neurons and motor neurons respectively. There is still no cure or effective treatment against the disease progression and most of the treatments are symptomatic. The present review offers an overview of the different factors involved in the pathogenesis of these diseases. Subsequently, we focused on the recent advanced studies of dietary polyphenols and stem cell therapies, which have made it possible to slow down the progression of neurodegeneration. To date, stem cells and different polyphenols have been used for the directional induction of neural stem cells into dopaminergic neurons and motor neurons. We have also discussed their involvement in the modulation of different signal transduction pathways and growth factor levels in various in vivo and in vitro studies. Likewise stem cells, polyphenols also exhibit the potential of neuroprotection by their anti-apoptotic, anti-inflammatory, anti-oxidant properties regulating the growth factors levels and molecular signaling events. Overall this review provides a detailed insight into recent strategies that promise the use of polyphenol with stem cell therapy for the possible treatment of PD and ALS.

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